Convenient one-pot synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives via solvent-free five-component condensation reactions

Article abstract of DOI:10.1007/s11164-014-1758-7

N-Acyl-1,3-diaryl-2-azaphenalene derivatives have been synthesized by one-pot condensation reaction of aromatic aldehydes, 2,7-naphthalenediol, carboxylic acids, and aqueous ammonia (25 %). Different aromatic aldehydes and carboxylic acids have been used

Full text of DOI:10.1007/s11164-014-1758-7

Res Chem Intermed
DOI 10.1007/s11164-014-1758-7
Convenient one-pot synthesis of N-acyl-1,3-diaryl-2-
azaphenalene derivatives via solvent-free five-
component condensation reactions
•
Akbar Mobinikhaledi Naser Foroughifar
•
•
Hassan Moghanian Reza Mozaffari
Received: 30 March 2014 / Accepted: 21 June 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract N-Acyl-1,3-diaryl-2-azaphenalene derivatives have been synthesized by
one-pot condensation reaction of aromatic aldehydes, 2,7-naphthalenediol, carboxylic
acids, and aqueous ammonia (25 %). Different aromatic aldehydes and carboxylic acids
have been used in the reaction and the products were always obtained in good to high
yields. The method is simple, solvent free, and involves a short reaction time. These
relatively rapid reactions possibly proceed via a Betti reaction mechanism.
Keywords 2-Azaphenalene Á 2,7-Naphthalenediol Á One-pot Á Multi-component Á
Solvent-free
Introduction
Multicomponent reactions (MCRs) are important in modern organic synthesis
because they can introduce additional diversity into a molecule in a one pot reaction
[1–4]. Some major advantages of MCRs are atom-economy, convergent character,
operational simplicity, structural diversity, and complexity of the molecules. These
reactions are also increasingly important in combinatorial chemistry and drug
discovery [5, 6]. In the history of multicomponent one-pot reactions, the Strecker
synthesis, which led to a-aminonitriles, was the first to be studied [7]. Subsequently,
there has been substantial development of this MCR procedure. Mention may be
made of the Biginelli [8], Passerini [9], Ugi [10], and Mannich [11] reactions. The
Mannich reaction, aminoalkylation of aldehydes in which C–N and C–C single
A. Mobinikhaledi Á H. Moghanian (&) Á R. Mozaffari
Department of Chemistry, Faculty of Science, Arak University, Arak 38156-879, Iran
e-mail: moghanian@gmail.com
N. Foroughifar
Faculty of Chemistry, Islamic Azad University, North Branch, Tehran, Iran
123

A. Mobinikhaledi et al.
bonds replace the C=O double bond, is one of the most important MCRs in organic
synthesis [12].
The Betti reaction [13] is a Mannich-type reaction for synthesis of a-
aminobenzylnaphthol derivatives in which an aromatic aldehyde, ammonia, and
2-naphthol are combined in one pot procedure [14]. This reaction has been
developed by using different N sources, substituted benzaldehydes or formal-
dehyde [15, 16], and 1-naphthol [17]. The order and nature of these compounds
substantially determine the reaction conditions and the method of isolation of
the Mannich product [18]. Because of the potential utility of Mannich-type
phenolic bases, particular attention has been devoted to aminoalkylation of
naphthol derivatives [19–21], which can be used as intermediates for synthesis
of derivatives with substantial antibacterial, hypotensive, and bradycardiac
activity [22]. Their phenolic hydroxyl groups and amino groups can be used to
develop several synthetic building blocks [23]. Furthermore, optically active
Betti bases can be used as chiral catalysts in enantioselective transformations
[14].
Azaphenalenyl, a heteroatomic modification of the phenalenyl system, is an
important building block in the synthesis of organic multifunctional electronic and
magnetic materials [24–26]. Azaphenalene derivatives have very low oxidation
potentials and very low negative reduction potentials and are, thus, extremely
promising antioxidants in biological systems [27]. Several alkaloid-based com-
pounds with a tricyclic azaphenalene core have been isolated from a variety of
ladybird species; the most prominent of these are precoccinelline, myrrhine, and
hippodamine [28]. Because of their high biological activity, scarce natural supply,
and difficult, only small-scale, isolation from natural sources, synthesis of this
heterocyclic nucleus is currently of major importance.
We have developed a facile, rapid, and efficient method for synthesis of N-
acyl-1,3-diaryl-2-azaphenalene derivatives in good to high yield via a catalyst-free
five-component condensation reaction under solvent-free classical heating
conditions.
Experimental
General
All chemicals were purchased from Merck or Fluka and used without further
purification. Melting points were measured in capillary tubes on an electro thermal
digital apparatus and are uncorrected. Known products were identified by
comparison of their melting points and spectral data with those reported in the
literature. FTIR spectra were recorded on a Unicom Galaxy Series FT-IR 5000
spectrophotometer in the region 4,000–400 cm-1, using pressed KBr discs. NMR
spectra were recorded on Bruker Avance spectrophotometer (300 MHz), in DMSO-
d6, using TMS as internal standard. Elemental analysis was performed with a Vario
EL III elemental analyzer.
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One-pot synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives
General procedure for preparation of N-acyl-1,3-diaryl-2-azaphenalene
derivatives (5a–5p)
A mixture of 2,7-naphthalenediol (1 mmol), aldehyde (2 mmol), carboxylic acid
(1.2 mmol), and aqueous ammonia (0.2 mL, 25 %) was stirred under solvent-free
conditions at 120 °C for an appropriate time (indicated in Table 2). The progress of
the reaction was monitored by TLC. After completion of the reactions, saturated
aqueous NaCl (20 mL) was added, the suspension was stirred for 30 min, and the
precipitate was isolated by filtration, washed with water, and air-dried. The crude
products were washed with ethyl acetate–n-hexane, (20 mL, 1:4) to afford the pure
products.
Characterization data for new compounds
Compound 5b (Table 2, entry 2)
IR (KBr): mmax = 3371, 3076, 2864, 1626, 1526, 1512, 1424, 1346, 1321, 1275,
1
1156, 1024, 832, 699 cm-1; H NMR (300 MHz, DMSO-d6): d = 5.30 (s, 2H),
6.91 (d, J = 8.8 Hz, 2H), 7.67–7.48 (m, 9H), 7.94 (s, 4H), 8.08 (d, J = 7.6 Hz, 2H),
9.45 (s, 2H, disappeared on D2O exchange); 13C NMR(75 MHz, DMSO-d6):
d = 53.5, 114.9, 115.4, 122.0, 122.8, 123.0, 128.5, 129.0, 129.7, 131.3, 131.7,
133.2, 135.4, 147.2, 148.1, 150.9, 167.9; Anal calcd. for C31H21N3O7: C, 68.00; H,
3.87; N, 7.67. Found: C, 67.85; H, 3.98; N, 7.53.
Compound 5f (Table 2, entry 6)
IR (KBr): mmax = 3319, 3211, 3015, 2823, 2696, 1632, 1604, 1543, 1516, 1429,
1
1309, 1248, 1174, 1130, 831, 773, 657 cm-1; H NMR (300 MHz, DMSO-d6):
d = 1.90 (s, 3H), 5.32 (s, 2H), 6.60–6.50 (m, 4H), 6.95–6.84 (m, 6H), 7.53 (d,
J = 7.4 Hz, 2H), 8.92 (br, 4H, disappeared on D2O exchange); 13C NMR(75 MHz,
DMSO-d6): d = 22.1, 53.3, 115.0, 115.3, 116.0, 122.6, 127.7, 129.4, 132.0, 134.2,
150.7, 156.4, 173.0; Anal calcd. for C26H21NO5: C, 73.06; H, 4.95; N,3.28. Found:
C, 72.86; H, 4.81; N, 3.16.
Compound 5g (Table 2, entry 7)
IR (KBr): mmax = 3250–2420, 2362, 1626, 1512, 1433, 1330, 1273, 1080, 881, 765,
1
700, 634 cm-1; H NMR (300 MHz, DMSO-d6): d = 0.99 (t, J = 7.5 Hz, 3H),
2.21 (q, J = 7.5 Hz, 2H), 5.18 (s, 2H), 6.85 (d, J = 8.7 Hz, 2H), 7.08 (d,
J = 7.5 Hz, 4H), 7.13–7.7.24 (m, 6H), 7.57 (d, J = 8.7 Hz, 2H), 9.18 (br, 2H,
disappeared on D2O exchange); 13C NMR (75 MHz, DMSO-d6): d = 9.6, 27.4,
53.9, 115.2, 116.3, 122.8, 126.6, 127.7, 128.2, 128.3, 132.2, 145.0, 150.5, 175.8;
Anal calcd. for C27H23NO3: C, 79.20; H, 5.66; N, 3.42. Found: C, 79.35; H, 5.53; N,
3.51.
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A. Mobinikhaledi et al.
Compound 5h (Table 2, entry 8)
IR (KBr): mmax = 3086, 2974, 2883, 2702, 2621, 1626, 1604, 1512, 1438, 1332,
1
1232, 1161, 1080, 833, 781, 626 cm-1; H NMR (300 MHz, DMSO-d6): d = 0.98
(t, J = 7.5 Hz, 3H), 2.18 (q, J = 7.5 Hz, 2H), 5.15 (s, 2H), 6.85 (d, J = 8.7 Hz,
2H), 7.00–7.10 (m, 8H), 7.57 (d, J = 8.7 Hz, 2H), 9.21(br, 2H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 9.6, 27.4, 53.2, 114.9, 115.3,
116.1, 122.8, 127.9, 130.2, 132.0, 141.1, 150.6, 162.9, 175.7; Anal calcd. for
C27H21F2NO3: C, 72.80; H, 4.75; N, 3.14. Found: C, 72.91; H, 4.81; N, 3.06.
Compound 5i (Table 2, Entry 9)
IR (KBr): mmax = 3350–2840, 2706, 1631, 1595, 1514, 1460, 1282, 1240, 1051,
1
831, 744 cm-1; H NMR (300 MHz, DMSO-d6): d = 0.99 (t, J = 7.5 Hz, 3H),
2.21 (q, J = 7.5 Hz, 2H), 5.69 (s, 2H), 5.92–6.03 (m, 4H), 6.34 (d, J = 7.9 Hz, 2H),
6.59 (t, J = 7.5 Hz, 2H), 6.99 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 9.44
(br, 4H, disappeared on D2O exchange); 13C NMR (75 MHz, DMSO-d6): d = 10.2,
28.7, 49.6, 111.3, 114.9, 115.0, 117.6, 122.5, 124.8, 127.9, 128.7, 128.9, 130.7,
151.8, 157.1, 177.3; Anal calcd. for C27H23NO5: C, 73.46; H, 5.25; N, 3.17. Found:
C, 73.32; H, 5.15; N, 3.26.
Compound 5j (Table 2, entry 10)
IR (KBr): mmax = 3063, 2980, 2885, 2822, 2650, 1626, 1595, 1512, 1421, 1323,
1269, 1238, 1132, 1074, 881, 835, 787, 690, 632 cm-1 1H NMR (300 MHz,
;
DMSO-d6): d = 0.98 (t, J = 7.5 Hz, 3H), 2.21 (q, J = 7.5 Hz, 2H), 5.15 (s, 2H),
6.88 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 7.2 Hz, 2H), 7.18–7.24 (m, 4H), 7.37 (d,
J = 7.8 Hz, 2H), 7.61 (d, J = 8.8 Hz, 2H), 9.33 (s, 2H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 9.6, 27.4, 53.6, 115.3, 115.5,
121.6, 122.7, 127.5, 128.1, 129.5, 130.5, 130.9, 131.8, 147.9, 150.7, 175.7; Anal
calcd. for C27H21Br2NO3: C, 57.17; H, 3.73; N, 2.47. Found: C, 57.23; H, 3.87; N,
2.55.
Compound 5k (Table 2, entry 11)
IR (KBr): mmax = 3065, 2966, 2877, 2793, 2715, 2642, 1624, 1514, 1411, 1329,
1
1257, 1085, 833, 765, 698 cm-1; H NMR (300 MHz, DMSO-d6): d = 0.85 (t,
J = 7.4 Hz, 3H), 1.04 (d, J = 7.0 Hz, 3H), 1.34–1.43 (m, 1H), 1.51–1.58 (m, 1H),
2.22–2.28 (m, 1H), 5.18 (s, 2H), 6.86 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 7.4 Hz, 4H),
7.13–7.24 (m, 6H), 7.57 (d, J = 8.7 Hz, 2H), 9.18 (br, 2H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 11.9, 17.0, 26.7, 40.6, 53.9, 115.2,
116.3, 122.8, 126.6, 127.7, 128.2, 128.3, 132.2, 145.1, 150.6, 177.9; Anal calcd. for
C29H27NO3: C, 79.61; H, 6.22; N, 3.20. Found: C, 79.50; H, 6.35; N, 3.15.
123

One-pot synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives
Compound 5l (Table 2, entry 12)
IR (KBr): mmax = 3265–2500, 1626, 1593, 1516, 1410, 1329, 1049, 883, 831,
686 cm-1; 1H NMR (300 MHz, DMSO-d6): d = 0.85 (t, J = 7.4 Hz, 3H), 1.05 (d,
J = 7.0 Hz, 3H), 1.34–1.45 (m, 1H), 1.48–1.61 (m, 1H), 2.20–2.26 (m, 7H), 5.14 (s,
2H), 6.84 (d, J = 8.5 Hz, 2H), 6.94–7.03 (m, 8H), 7.55 (d, J = 8.5 Hz, 2H), 9.16
(br, 2H, disappeared on D2O exchange); 13C NMR (75 MHz, DMSO-d6): d = 11.9,
17.0, 21.1, 26.7, 40.71, 53.6, 115.2, 116.5, 122.8, 127.6, 128.3, 128.8, 132.2, 135.5,
142.0, 150.5, 177.9; Anal calcd. for C31H31NO3: C, 79.97; H, 6.71; N, 3.01. Found:
C, 80.11; H, 6.59; N, 2.95.
Compound 5m (Table 2, entry 13)
IR (KBr): mmax = 3464–2885, 2681, 1631, 1589, 1512, 1454, 1388, 1313, 1089,
1
1012, 829, 775, 694 cm-1; H NMR (300 MHz, DMSO-d6): d = 5.50 (s, 2H),
6.68–6.75 (m, 10H), 7.00 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.69 (d,
J = 8.7 Hz, 2H), 7.93 (d, J = 8.1 Hz, 2H), 9.43 (br, 2H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 52.8, 113.7, 114.8, 122.7, 125.7,
126.9, 128.3, 128.8, 128.9, 131.0, 131.5, 131.9, 137.4, 141.9, 151.3, 167.5; Anal
calcd. for C31H22ClNO3: C, 75.68; H, 4.51; N, 2.85. Found: C, 75.77; H, 4.58; N,
2.78.
Compound 5n (Table 2, entry 14)
IR (KBr): mmax = 3530–2837, 2714, 2584, 1633, 1591, 1516, 1460, 1394, 1278,
1095, 885, 831, 748 cm-1; 1H NMR (300 MHz, DMSO-d6): d = 5.84 (s, 2H), 5.93
(d, J = 7.5 Hz, 2H), 6.06 (t, J = 7.3 Hz, 2H), 6.43 (d, J = 7.9 Hz, 2H), 6.63 (t,
J = 7.5 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.77 (d,
J = 8.8 Hz, 2H), 8.00 (d, J = 8.2 Hz, 2H), 10.00 (br, 4H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 49.9, 109.6, 115.0, 115.1, 117.9,
122.4, 123.3, 128.4, 128.5, 128.9, 129.4, 130.3, 131.6, 135.8, 135.9, 152.3, 156.7,
169.9; Anal calcd. for C31H22ClNO5: C, 71.06; H, 4.23; N, 2.67. Found: C, 69.90;
H, 4.32; N, 2.75.
Compound 5o (Table 2, entry 15)
IR (KBr): mmax = 3460–2818, 2671, 2521, 1620, 1591, 1539, 1516, 1433, 1388,
1319, 1273, 835, 761, 700 cm-1; 1H NMR (300 MHz, DMSO-d6): d = 2.36 (s,
3H), 5.19 (s, 2H), 6.87 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 7.2 Hz, 4H), 7.14–724 (m,
6H), 7.34–7.43 (m, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 9.20
(br, 2H, disappeared on D2O exchange); 13C NMR (75 MHz, DMSO-d6): d = 21.4,
54.1, 115.3, 122.7, 127.0, 128.1, 128.3, 128.7, 128.8, 129.7, 130.3, 132.1, 132.6,
132.9, 133.4, 138.1, 143.9, 151.0, 168.4; Anal calcd. for C32H25NO3: C, 81.51; H,
5.34; N, 2.97. Found: C, 81.36; H, 5.21; N, 2.90.
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A. Mobinikhaledi et al.
Compound 5p (Table 2, entry 16)
IR (KBr): mmax = 3489–2816, 2677, 1626, 1602, 1512, 1379, 1319, 1226, 1163,
1
835, 761 cm-1; H NMR (300 MHz, DMSO-d6): d = 2.36 (s, 3H), 5.18 (s, 2H),
6.88 (d, J = 8.7 Hz, 2H), 7.01–7.11 (m, 8H), 7.34–7.43 (m, 2H), 7.59 (d,
J = 8.7 Hz, 2H), 7.76 (d, J = 8.6 Hz, 2H), 9.20 (br, 2H, disappeared on D2O
exchange); 13C NMR (75 MHz, DMSO-d6): d = 21.3, 53.2, 114.7, 115.3, 115.8,
122.7, 126.9, 127.9, 128.8, 130.1, 130.2, 131.7, 131.9, 133.7, 138.2, 140.7, 150.7,
162.9, 168.1; Anal calcd. for C32H23F2NO3: C, 75.73; H, 4.57; N, 2.76. Found: C,
75.52; H, 4.63; N, 2.70.
N-((2,7-Dihydroxynaphthalen-1-yl)(phenyl)methyl)benzamide (Compound 6)
IR (KBr): mmax = 3425, 3225–2550, 1629, 1580, 1518, 1323, 1219, 1060, 837, 727,
638 cm-1; 1H NMR (300 MHz, DMSO-d6): d = 6.90 (s, 1H), 7.02 (d, J = 8.6 Hz,
1H), 7.15–7.21 (m, 2H), 7.26–7.38 (m, 4H), 7.47–7.56 (m, 4H), 7.68 (t, J = 8.6 Hz,
2H), 7.87 (d, J = 7.0 Hz, 2H), 9.01 (s, 1H), 9.76 (s, 1H), 10.33 (s, 1H); 13C NMR
(75 MHz, DMSO-d6): d = 49.9, 104.7, 115.7, 117.7, 123.5, 126.9, 127.0, 127.4,
127.9, 128.7, 129.1, 129.7, 130.8, 131.9, 134.6, 134.8, 142.7, 153.9, 156.9, 166.0;
Anal calcd. for C24H19NO3: C, 78.03; H, 5.18; N, 3.79. Found: C, 77.90; H, 5.25; N,
3.68.
Results and discussion
We recently reported a simple and efficient method of synthesis of 1,3-diphenyl-2-
azaphenalene [29] and N-acyl-1,3-diphenyl-2-azaphenalene derivatives [30] via a
Betti-type reaction in which 2-naphthol was replaced by 2,7-naphthalenediol. These
good results prompted us to further investigate the reaction of aldehydes, 2,7-
naphthalenediol, and ammonia. In continuation of our efforts to develop synthetic
methods for important transformations [31–34], we now report a simple and
efficient procedure for synthesis of new N-acyl-1,3-diaryl-2-azaphenalene deriva-
tives by condensation of 2,7-naphthalenediol, aromatic aldehydes, carboxylic acids,
and aqueous ammonia (25 %) under solvent-free conditions (Scheme 1).
To optimize the reaction conditions, reaction of benzaldehyde 2a (1 mmol), 2,7-
naphthalenediol 1, benzoic acid 3a, and aqueous ammonia (25 %) was used as a
model, and was conducted under different reaction conditions, for example solvent
and temperature. Initially, the model reaction was conducted in several solvents
(ethanol, chloroform, 1,4-dioxane, tetrahydrofuran, dimethylformamide, and tolu-
ene) and under solvent-free conditions to investigate the effect of solvents. As
shown in Table 1, it was found that conventional heating (at 120 °C) under solvent-
free conditions is more efficient than use of organic solvents in respect of reaction
time and yield of the desired azaphenalene 5a (Table 1, entry 9). When the same
reaction was conducted at room temperature or at 70 °C, yields were low.
Increasing the reaction temperature to 140 °C did not increase yield of the product
(Table 1).
123

One-pot synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives
Scheme 1 Synthesis of N-acyl-1,3-diphenyl-2-azaphenalene derivatives
Table 1 Optimization of the conditions for synthesis of N-benzoyl-1,3-diphenyl-4,9-dihydroxy-2,3-
dihydro-2-azaphenalene (Table 2, entry 1)
Entry
Solvent
Conditions
Time (h)
Yield (%)a
1
2
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
RT
10
10
10
10
10
10
5
86
\10
35
CHCl3
3
1,4-Dioxane
THF
4
15
5
DMF
0
6
Toluene
\10
0
7
Solvent-free
Solvent-free
Solvent-free
Solvent-free
8
70 °C
120 °C
140 °C
1
23
9
0.25
0.25
89
10
85
Benzaldehyde (2 mmol), 2,7-naphthalenediol (1 mmol), benzoic acid (1.2 mmol), and aqueous ammonia
(0.2 mL, 25 %)
a
Isolated yields
Reaction of 2,7-naphthalenediol with a variety of aromatic aldehydes, benzoic acid,
and ammonia was performed under solvent-free conditions at 120 °C and afforded the
corresponding N-acyl-1,3-diaryl-2-azaphenalene derivatives in good to high yields
(Table 2). The scope of the reaction with regard to aromatic aldehydes was examined,
and it was found that substituents, for example electron-withdrawing groups and
electron-donating groups, could tolerate the reaction conditions. However, when
aliphatic aldehydes, for example propionaldehyde and isobutyraldehyde, were used in
123

A. Mobinikhaledi et al.
Table 2 Synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives under solvent-free conditions
Entry Ar (2)
R (3)
Product Time Yield (%)a M.p. (°C)
(min)
Found
Reported [Ref.]
1
C6H5
C6H5
5a
5b
5c
5d
5e
5f
15
20
15
10
10
15
10
15
15
10
10
15
15
15
10
10
89
80
87
88
90
82
85
79
83
80
87
74
80
81
74
72
215–217 214–215 [30]
198–199
2
3-NO2C6H4 C6H5
–
3
4-ClC6H4
C6H5
C6H5
218–220 219–221 [30]
208–209 207–208 [30]
217–219 219–220 [30]
4
CH3
5
3-BrC6H4
4-OHC6H4
C6H5
CH3
6
CH3
216–217
212–214
200–201
248–250
180–181
200–202
190–191
231–232
262–263
203–205
218–220
–
–
–
–
–
–
–
–
–
–
–
7
CH3CH2
CH3CH2
CH3CH2
CH3CH2
5g
5h
5i
8
4-FC6H4
2-OHC6H4
3-BrC6H4
C6H5
9
10
11
12
13
14
15
16
a
5j
CH3CH2CH(CH3) 5k
CH3CH2CH(CH3) 5l
4-MeC6H4
C6H5
4-ClC6H4
4-ClC6H4
3-MeC6H4
3-MeC6H4
5m
5n
5o
2-OHC6H4
C6H5
4-FC6H4
5p
Isolated yields
this procedure under the above optimized conditions, only trace amounts of product
were detected.
To investigate the generality of the reaction, different aldehydes with either
electron-donating or electron-withdrawing groups were reacted with structurally and
electronically diverse carboxylic acids, 2,7-naphthalenediol, and aqueous ammonia
(25 %) under the optimized reaction conditions; the results are summarized in
Table 2. All reactions proceeded efficiently at 120 °C and the desired products were
obtained in good to high yields (72–90 %) in relatively short reaction times, without
formation of any side products. As is apparent from Table 2, the procedure was
highly effective and the nature of substituents on the aromatic ring of aldehydes did
not have obvious effects in terms of yields and times under the reaction conditions.
To study mechanistic aspects of this multi-component reaction, reaction of
benzaldehyde with 2,7-naphthalenediol, benzoic acid, and ammonia was used as
model reaction. First, we attempted to explain the reaction on the basis of formation
of benzamide from ammonia and benzoic acid at 120 °C. Therefore, reaction of 2,7-
naphthalenediol with benzaldehyde, and benzamide was performed under solvent-
free conditions at 120 °C, similar to use of 2-naphthol in the synthesis of amidoalkyl
naphthols [35–37], but the reaction was unsuccessful and only the corresponding
amidoalkyl naphthol 6 was obtained (Scheme 2). When reaction of 2,7-naphtha-
lenediol, benzaldehyde, and ammonia under solvent-free conditions at 120 °C was
investigated 1,3-diaryl-2-azaphenalene derivatives 7 were obtained as isolable
intermediates [29] (Scheme 2).
123

One-pot synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives
Scheme 2 Condensation of 2,7-naphthalenediol and aldehyde with amide or ammonia
Scheme 3 A plausible mechanism for synthesis of N-acyl-1,3-diaryl-2-azaphenalene derivatives
These results suggest formation of the desired products can be explained on the
basis of the Betti reaction [13]. 2,7-Naphthalenediol may produce naphthoxazine
I or isomeric Schiff base II, similar to 2-naphthol in the Betti reaction. Because of
the tautomerism of these condensation products [15, 16], the Schiff base
intermediate furnished the 1,3-diaryl-2-azaphenalene derivatives on intermolecular
cyclization and keto–enol tautomerization (Scheme 3). This intermediate IV can be
converted to intermediate V and reacted with benzoic acid to produce intermediate
VI (an explanation of this behavior might be that the aromatic Mannich reaction is a
reversible reaction [38]). Finally the expected products VIII were afforded by
intermolecular acylation of VI and intermolecular ring-closure reaction of
intermediate VII.
Conclusion
In conclusion, we have described a new, efficient, one-pot method for synthesis of
N-acyl-1,3-diaryl-2-azaphenalene derivatives by five-component cyclo-condensa-
tion reaction of 2,7-naphthalenediol, aromatic aldehydes, carboxylic acids, and
123

A. Mobinikhaledi et al.
aqueous ammonia (25 %) under solvent-free conditions at 120 °C. In addition to the
efficiency and simplicity of this catalyst-free procedure, advantages include ease of
workup, good to high yields of products, and environmental friendliness.
Acknowledgments We gratefully acknowledge financial support from the Research Council of Arak
University.
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